Deep Brain Stimulation (DBS) for Depression: Long-Term Followup

Is deep brain stimulation (DBS) an effective treatment for chronic, treatment-resistant depression?

According to a new study, it is. But sadly, without a control group, the researchers can’t really say whether it was their treatment — DBS — that helped people with their depression, or whether it was simply the passage of time. Furthermore, the study did not show that actual DBS treatment is more effective than placebo treatment — so-called “sham” treatment (where a patient undergoes the procedure, but nothing is activated afterward).

This last point is important, because other studies conducted on other alternative depression brain treatments have shown mixed results when it comes to comparing them to placebos. In multiple studies, researchers have found no significant differences between the real treatment and the placebo or sham treatment.

In the new study (Kennedy et al., 2011) about deep brain stimulation (DBS), Canadian researchers for up to 6 years followed 20 patients who received the procedure. DBS involves brain surgery — placing electrodes within the brain to deliver continuous electrical pulse stimulation. Why it works remains a mystery, although various theories have been offered over the years. But it’s been used for years to help treat severe Parkinson’s disease, to varying degrees of success.

Researchers were interested in the long-term safety of the device, as well as its efficacy — measured by both a response on the Hamilton Depression Rating Scale (called the HAM-D; the researchers defined a “response” as a reduction of 50% or greater in HAM-D score) or remission (HAM-D score equal to or less than 7).

Response rates in years 1, 2, 3 and last followup were found to be 62.5, 46.2, 75 and 64.3 percent, respectively. The researchers had no explanation why in Year 2, response rates took such a significant and serious dive. Which is a problem — if DBS is intended as a stable and reliable treatment for chronic, serious depression, it can’t have changes in depression of between 50 and 100 percent over the course of a year’s time. That’s a significantly variable depressed mood.

Remission rates generally fared worse — this is the measure that the person is basically living life depression-free. In Years 1, 2, 3 and last followup, remission rates were 18.8, 15.4, 50, and 42.9 percent. Again, the researchers offer little explanation why the significant jump in the rates from Year 2 to Year 3, leaving me scratching my head about the 300% change in this number. As the authors note, compared to a naturalistic study of antidepressants for treatment-resistant depression — 8 percent — these remission rates are very good, though.

One alternative hypothesis that should be considered is that DBS, in fact, really doesn’t have much to do with a person’s mood so many years after treatment. It could simply be the effects of time alone — without a control group, we simply don’t really know what are the effects of the treatment, and what are the effects of other variables, such as time.

It should be noted, too, that 15 percent of the experimental group died over the course of this study — one person died of natural causes, but two people died of suicide. Two others had suicide attempts. This translates into 20 percent of the group who “successfully” underwent DBS treatment to still have serious suicidal thoughts and behaviors. Both people who committed suicide also met study criteria for remission of their depression. This makes little sense — if depression has remitted, why commit suicide? The researchers attribute the suicides to the “high rates of mortality associated with treatment-resistant depression.” The researchers did not seem to really consider the alternative hypothesis — that the DBS actually contributed to or caused the suicides and suicidal ideation (as we’ve seen with certain other treatments).

Can You Do Sham Treatment with DBS?

Sham treatment with surgery is not ethically possible — you cannot perform invasive brain surgery and then do nothing to treat the individual. However, researchers don’t immediately turn on the pulse generator after surgery. The patient is given some time to heal, and the pulse generator remains off and disconnected from the leads leading to the electrodes implanted within the brain. Researchers can design an experiment (and have in some small studies) where they tell one group of patients they are turning the pulse generator on when in fact they do not.

I’m not sure how effective a “sham” this is, however. It is not uncommon for a patient to become well familiarized with the procedure they are about to undergo. It took me about 5 minutes of Internet searching to discover the basics of DBS — the surgery, the recovery period, the testing with the pulse generator. A patient who feels nothing after the pulse generator has been supposedly turned on in a sham treatment may become suspicious.

Why is this important? Because we know from other brain treatments — repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) — that sham treatments have been shown to be as effective or nearly as effective as the active, real treatment. It seems that just the idea of treatment and going through the motions is enough to convince many people to start to feel better.

We’ve also seen this placebo effect all too well in recent years in re-analysis of data of certain psychiatric medications’ effectiveness. When researchers looked more closely at some of the raw data, they discovered that some psychiatric medications may be overstating their effectiveness over a sugar pill (placebo).

Conclusions

I’m anxious for alternative depression treatments to become more widely available. While I think psychotherapy is a powerful treatment for depression, too many people are simply resistant to trying it, or try it and don’t have a good match with a professional, and so give up on it too soon. Antidepressants have also been shown to be effective, despite the placebo research mentioned above (some of the research was done on data sets from decades ago and since that time, we’ve had a lot of new research to support their continued use).

Wouldn’t it be nice to have more modern brain tools in our arsenal (rather than the archaic and non-FDA approved ECT)? I think so, especially for these cases of serious, chronic, unremitting depression where both drugs and psychotherapy have failed.

Unfortunately, I’m not sure deep brain stimulation is quite there yet. While seemingly effective, there are still many unanswered questions that researchers haven’t yet provided satisfactory answers. I might consider DBS over ECT, because its side effect profile appears to be better — there were no adverse events reported in the current study.

References

Benninger, David H.; Lomarev, Mikhail; Lopez, Grisel; Wassermann, Eric M.; Li, Xiaobai; Considine, Elaine; Hallett, Mark; (2010). Transcranial direct current stimulation for the treatment of Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 81(10), 1105-1111.

Kennedy et al. (2011). Deep Brain Stimulation for Treatment-Resistant Depression: Follow-Up After 3 to 6 years.. Am J Psychiatry.

Loo, Colleen K.; Sachdev, Perminder; Martin, Donel; Pigot, Melissa; Alonzo, Angelo; Malhi, Gin S.; Lagopoulos, Jim; Mitchell, Philip; (2010). A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression. International Journal of Neuropsychopharmacology, 13(1), 61-69.

Triggs, William J.; Ricciuti, Nikki; Ward, Herbert E.; Cheng, Jing; Bowers, Dawn; Goodman, Wayne K.; Kluger, Benzi M.; Nadeau, Stephen E.; (2010). Right and left dorsolateral pre-frontal rTMS treatment of refractory depression: A randomized, sham-controlled trial. Psychiatry Research, 178(3), 467-474.